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相关概念视频

GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
GPCR Desensitization01:12

GPCR Desensitization

G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
G Protein-coupled Receptors01:15

G Protein-coupled Receptors

G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
Transducer Mechanism: G Protein–Coupled Receptors01:30

Transducer Mechanism: G Protein–Coupled Receptors

G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
GPCRs are also called heptahelical, 7TM, or...
G-protein Coupled Receptors01:21

G-protein Coupled Receptors

G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
G-protein Coupled Receptors01:21

G-protein Coupled Receptors

G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.

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相关实验视频

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Monitoring GPCR-&#946;-arrestin1/2 Interactions in Real Time Living Systems to Accelerate Drug Discovery
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Published on: June 28, 2019

GPCR工程产生了对β2-上腺素受体功能的高分辨率结构洞察力.

Daniel M Rosenbaum1, Vadim Cherezov, Michael A Hanson

  • 1Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA.

Science (New York, N.Y.)
|October 27, 2007
PubMed
概括

研究人员设计了一种β2-上腺素受体 (β2AR) 融合蛋白,β2AR-T4L,以研究其结构. 这种工程受体保留了药理性质,为G蛋白合受体 (GPCR) 功能和连接体结合提供了洞察力.

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High-resolution Spatiotemporal Analysis of Receptor Dynamics by Single-molecule Fluorescence Microscopy
15:13

High-resolution Spatiotemporal Analysis of Receptor Dynamics by Single-molecule Fluorescence Microscopy

Published on: July 25, 2014

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科学领域:

  • 生物化学 生物化学
  • 分子生物学分子生物学
  • 结构生物学 结构生物学

背景情况:

  • β2-上腺素受体 (β2AR) 是一个关键的G蛋白合受体 (GPCR),参与细胞信号传输.
  • GPCR表现出结构灵活性,对高分辨率结构研究构成挑战.
  • 了解β2AR结构对于破译它与配体和下游信号合作伙伴的相互作用至关重要.

研究的目的:

  • 为结构分析设计一种稳定的β2AR融合蛋白.
  • 研究beta2AR.的联结机制和形状变化.
  • 阐明β2AR激活和G蛋白合的结构基础.

主要方法:

  • 一种β2AR融合蛋白与T4溶酶 (β2AR-T4L) 的工程.
  • 融合蛋白的药理性质的表征.
  • 对beta2AR-T4L和结突变体的高分辨率结构数据的分析.

主要成果:

  • 工程化β2AR-T4L蛋白显示出接近原生药理特征.
  • 结构分析揭示了对受体内逆激动剂结合的洞察力.
  • 确定了一种相互作用网络,将连接连接体结合口袋与G蛋白相互作用部位连接起来.

结论:

  • β2AR-T4L融合蛋白是研究GPCR结构和功能的可行工具.
  • 提供了对连接体结合和形状变化的结构性见解.
  • 提出了一条连接连接连接器与G蛋白相互作用的构造途径.